Endocrine profile of β-thalassemia major patients followed from childhood to advanced adulthood in a tertiary care center

Abstract

Aim:Chronic iron overload resulting from frequent transfusions, poor compliance to efficient chelation therapy and chronic liver disease is basically responsible for the most severe complications of thalassemia major (TM). Before conventional treatment, TM was entirely childhood disease with a very short survival. Today, survival improved to 40–50 years and becomes a prevalent disease of adulthood and in the near future it will be one of senility. Furthermore, clinical phenotype of TM is changing with age and appearance of severe complications from the heart and endocrine glands that require special health care from well-informed specialists.Objectives:The aims of our study were to: (1) Imprint the clinical profile of long-lived TM patients; (2) evaluate retrospectively the cumulative incidence of endocrine diseases; (3) identify potential risk factors; and (4) orient the physicians in the modified clinical phenotype and the relative patients' health needs.Design:A retrospective cross-sectional study followed from childhood to adulthood by the same physician in a tertiary thalassemia clinic.Participants:Forty-three long-lived TM patients (mean age: 50.3 ± 10.8 years; range: 45.8–59.5 years; 23 females) were studied.Patients and Methods:An extensive medical history, with detailed clinical and laboratory data, endocrine complications, and current treatments, was obtained.Results:The data indicate that 88.4% of adult TM patients suffered from at least one endocrine complication. The majority of patients developed endocrine complications in the second decade of life when serum ferritin level was very high (12/23 TM female and 8/20 TM male patients, the serum ferritin levels at the diagnosis were above 5.000 ng/ml).Conclusions:These data underline that endocrine and bone complications in adult TM patients are highly prevalent and necessitate close monitoring, treatment, and follow-up. Physicians' strategies to optimize chelation therapy include identifying patients who are at risk for developing organ damage, developing chelation plans, promoting compliance, and educating patients. Several clinical aspects remain to be elucidated such as growth and impairment of glucose tolerance in relation to hepatitis C virus infection. Furthermore, affordable worldwide-established long-term treatment protocols for hypogonadism and osteoporosis are needed.

Endocrine Complications

“…[3] The incidence rate of hypogonadism, in both sexes, varies considerably between countries and much more between specialized centers, ranging from around 50% and may even approach 100%. [1][2][3][4] Hormone replacement therapy with sex steroids aims to relieve symptoms and signs of androgen or estrogens deficiency, using convenient and effective formulations of testosterone or estrogen/progesterone. Despite the large number of TM patients for whom HRT is prescribed, little prospective data exist to aid clinicians in making evidence-based decisions for the optimal treatment regimens.…”

“…This poor prognosis changed since the survival rates started to increase progressively thanks to the implementation of continuous and significant improvement of diagnostic and therapeutic methods, consisting mainly of an intensive transfusion program combined with chelation therapy and imaging methods. [1][2][3][4] Regular red blood cell (RBC) transfusions eliminate the complications of anemia, compensatory bone marrow expansion, bone changes and splenomegaly, restore the physiological growth throughout childhood and extend survival. The most serious disadvantage of life-saving transfusions is the inexorable accumulation of iron within tissues.…”

“…Other factors contributing to the variability of cellular iron overload are: a) the cell surface transferrin receptors and the capacity of the cells to deploy defence mechanisms against inorganic iron; b) individual susceptibility to iron toxic effect; c) the development of organ(s) damage secondary to persisting severe iron overload in the years preceding iron chelation therapy; and d) liver disorders, chronic hypoxia and associated endocrine complications. [1][2][3] Multi-transfused thalassemia major (TM) patients frequently develop severe endocrine complications mainly due to iron overload, anemia, and chronic liver disease, which require prompt diagnosis, treatment and close follow-up by specialists. [4] …”

Review and Recommendations on Management of Adult Female Thalassemia Patieνts With Hypogonadism Based on Literature Review and Experience of Icet-a Network Specialists

“…Multi-transfused thalassemia major (TM) patients frequently develop severe endocrine complications mainly due to iron overload, anemia, and chronic liver disease, which require prompt diagnosis, treatment and close follow-up by specialists 1–3…”

“…In adult females TM patients, hypogonadism is clinically diagnosed by the absence of pubertal development, or discontinuation or regression of the maturation of secondary sex characteristics due to pituitary dysfunction and/or gonadal damage, secondary to iron overload 4. The incidence rate of hypogonadism, in both sexes, varies considerably between countries and much more between specialized centers, ranging from around 50% and may even approach 100% 1–4…”